tetano
Editor, Senior Moderator
Cell Rep
. 2022 Apr 29;110829.
doi: 10.1016/j.celrep.2022.110829. Online ahead of print.
Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant
Yang Liu[SUP] 1 [/SUP], Jianying Liu[SUP] 2 [/SUP], Bryan A Johnson[SUP] 3 [/SUP], Hongjie Xia[SUP] 4 [/SUP], Zhiqiang Ku[SUP] 5 [/SUP], Craig Schindewolf[SUP] 2 [/SUP], Steven G Widen[SUP] 4 [/SUP], Zhiqiang An[SUP] 5 [/SUP], Scott C Weaver[SUP] 2 [/SUP], Vineet D Menachery[SUP] 2 [/SUP], Xuping Xie[SUP] 6 [/SUP], Pei-Yong Shi[SUP] 7 [/SUP]
Affiliations
Abstract
We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage.
Keywords: CP: Microbiology; Delta variant; S1/S2 cleavage; SARS-CoV-2; fitness; human airway culture; spike P681R; viral entry.
. 2022 Apr 29;110829.
doi: 10.1016/j.celrep.2022.110829. Online ahead of print.
Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant
Yang Liu[SUP] 1 [/SUP], Jianying Liu[SUP] 2 [/SUP], Bryan A Johnson[SUP] 3 [/SUP], Hongjie Xia[SUP] 4 [/SUP], Zhiqiang Ku[SUP] 5 [/SUP], Craig Schindewolf[SUP] 2 [/SUP], Steven G Widen[SUP] 4 [/SUP], Zhiqiang An[SUP] 5 [/SUP], Scott C Weaver[SUP] 2 [/SUP], Vineet D Menachery[SUP] 2 [/SUP], Xuping Xie[SUP] 6 [/SUP], Pei-Yong Shi[SUP] 7 [/SUP]
Affiliations
- PMID: 35550680
- DOI: 10.1016/j.celrep.2022.110829
Abstract
We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage.
Keywords: CP: Microbiology; Delta variant; S1/S2 cleavage; SARS-CoV-2; fitness; human airway culture; spike P681R; viral entry.